The goal of this proposed research is to determine the chemical mechanism of the metabolism of toxic and carcinogenic haloalkanes by cytochrome P-450 mixed function oxidase enzymes. Two classes of haloalkanes will be examined in vitro studies: l,l,l-trichloroethane compounds (2,2-(4'-chlorophenyl)-1,1,1-trichloroethane (DDT) and l,l,-trichloroethane (methylchloroform)) and l,2-dibromoalkanes(l,2-dibromoethane (ethylenedibromide) and tris-(2,3-dibromopropyl)phosphate (Tris)). Cytochrome P-450 metabolism of haloalkanes can result in detoxification or inactivation of the halocarbon (eg. l,l,l-trichloroethanes) or in bioactivation to the proximate agent (eg. l,2-dibromoalkanes) with resultant covalent binding to macromolecules. The products of the chemical and enzyme oxidation of these compounds and their iodinated analogs will be determined where not known. In addition, the nature of the chemically reactive intermediates formed in the chemical and enzymatic degradation of these halogenated compounds will be examined including the structures of products bound to protein and to DNA. A chemical mechanism for the metabolism of halocarbons by cytochrome P-450 will be experimentally evaluated which would enable the prediction of halocarbon metabolites and thereby of the potential toxicological significance of the parent halocarbon.